Souped-up ‘gene drives’ may help eliminate pests and diseases

A potentially life-saving technology that could eradicate diseases like Zika and malaria called a “gene drive” shouldn’t be released into the wild – for now. That’s the conclusion of a report released today by the US National Academies of Sciences

A gene drive is a piece of “selfish” DNA that can spread rapidly through a population. But fears that engineered gene drives could spread out of control may be exaggerated as there are flaws in the existing designs that mean they will not last long in the wild. However, New Scientist can reveal that souped-up versions are in the works that might just deliver on the technology’s enormous potential to do good – or bad.

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Most plants and animals have matching pairs of chromosomes, but pass down only one of each pair to an offspring – the other comes from the other parent. This means that if you add a piece of DNA to one chromosome, normally only half the offspring will inherit it.

Gene drives cheat by “copying and pasting” themselves to the other chromosome too, meaning all offspring inherit them and they can spread rapidly throughout a population. This happens even when the new DNA confers a disadvantage to the offspring – which is the very reason the technology is so beneficial to us.

Mosquito larvae are one target

Target Malaria

Engineer a gene drive to spread genes that stop mosquitoes carrying malaria, for instance, and you could eradicate the disease once and for all. A similar technique could also win the war on Zika virus.

However, one fear over this research is that experimental gene drives could escape from labs and begin to spread – perhaps with disastrous consequences, such as driving a beneficial species to extinction. Another fear is that if gene drives are deliberately released and turn out to have unintended consequences, there may be little we can do to stop them spreading.

In practice though, resistance to a gene drive often evolves in just a few generations, meaning these fears may be unfounded – for now anyway.

Andrea Crisanti’s team at Imperial College London, for instance, has been introducing gene drives into cages of mosquitoes, designed to destroy a gene needed for female fertility. While they initially spread fast, in some cases they have also begun to be lost after just a few generations. “This was anticipated,” says Crisanti.

Making problems

That’s because Crisanti, like many others, is using CRISPR gene editing to create the gene drives. For CRISPR-based gene drives to copy and paste themselves from one chromosome to another, they have to recognise a specific target DNA sequence, cut it, and splice a copy of themselves into the gap. But natural variation means that some organisms may have chromosomes in which the target DNA is different or missing. These naturally resistant chromosomes can spread through a population, making them immune to a specific gene drive.

Crisanti thinks this is what happened in his tests. One answer, he says, may be to pick target DNA sites that vary little between individuals. “We are already working on the second generation of drives,” he says.

But even targeting such “highly conserved” DNA sequences may not be enough. There is a more fundamental problem. The copy-and-paste process can go awry. Instead of a copy of a gene drive being pasted in after the target DNA is cut, the severed ends are sometimes crudely stuck back introducing mutations in the target DNA. In other words, even when naturally resistant chromosomes don’t exist, CRISPR gene drives can generate them.

According to a model developed by George Church’s team at Harvard University, this means that while existing CRISPR gene drives can spread rapidly at first, resistance will appear and the gene drive will disappear after a hundred generations or so.

Snip, snip, snip

But they have a cunning plan: to make the target DNA part of a crucial gene and to cut this gene in several places, not just one. By doing this, the crucial gene is destroyed. The gene drive includes the sequences needed to repair the gene. This means that if the copy and paste process works perfectly, the crucial gene is repaired along with the gene drive.

If the process goes awry and the ends are just stuck together, however, the gene containing the target DNA will be wrecked. Because it is crucial to the organism’s survival, the chromosome carrying it will not spread despite becoming resistant to the gene drive.

“That’s clever,” says Crisanti. “I like it very much.” But this approach will only work for adding genes to cells, not for destroying a specific gene as his team is doing, he points out. Nor does it solve the problem of gene drives evolving and changing as they spread.

So remains the big question of whether we should use gene drives at all. The potential benefits of effective gene drives are significant, the academy report concludes, but caution is needed. “There is insufficient evidence available at this time to support the release of gene-drive modified organisms into the environment.”